Women in their mid to late 30s and early 40s with infertility constitute the largest portion of the total infertility population. These women are also at an increased risk for pregnancy loss. This reflects a decline in oocyte quality and a diminished ovarian reserve as a result of follicular depletion. Ovarian reserve is a term that is used to describe the capacity of the ovary to provide eggs that are capable of fertilization resulting in a healthy and successful pregnancy.
While there is no gold standard for assessing the ovarian reserve of individual women, its indirect determination has been used to help direct infertility treatment.
Serum concentrations of follicle-stimulating hormone (FSH) and estradiol on day 3 of the menstrual cycle have been the tests of choice for assessing ovarian reserve. Cycle day 3 is chosen because at this time the estrogen concentration is expected to be low, a critical feature, as FSH concentrations are subject to negative feedback from estradiol. In general, day 3 FSH concentrations >20 to 25 IU/L are considered to be elevated and associated with poor reproductive outcome. FSH concentrations are expected to be below 10 IU/L in women with reproductive potential. Concomitant measurement of serum estradiol adds to the predictive power of an isolated FSH determination. Basal estradiol concentrations >75-80 pg/mL are associated with poor outcome.
Inhibin B is produced by the developing follicles and concentrations peak during the follicular phase. Concentrations of inhibin B can be used in conjunction with serum FSH and estradiol to assess ovarian function. As women age, serum FSH concentrations in the early follicular phase begin to increase. It has been suggested that this is due to a decline in the number of small follicles secreting inhibin B. Because inhibin is produced by the ovaries, it is thought to be a more direct marker of ovarian activity and ovarian reserve than FSH. In addition, cycle day 3 inhibin B concentrations may demonstrate a decrease before day 3 FSH concentrations.
Seifer et al reported that women undergoing in vitro fertilization (IVF) with day 3 inhibin B concentration <45 pg/mL had a pregnancy rate of 7% and a spontaneous abortion rate of 33% as compared to pregnancy rate of 26% and abortion rate of 3% in women with day 3 inhibin B concentrations of > 45 pg/mL.
In recent years, anti-Mullerian Hormone (AMH) has been suggested to be a more useful predictor of ovarian reserve. AMH is expressed by the granulosa cells of the ovary during the reproductive years, and controls the formation of primary follicles by inhibiting excessive follicular recruitment by FSH. In 2005 Tremellen reported that plasma AMH concentrations start to drop rapidly by age 30, and are ~10 pmol/L by the age of 37. David has blogged previously about the use of AMH as a predictor of IVF outcome.
Using a cut off value of 8.1 pmol/L, plasma AMH could predict poor ovarian reserve on a subsequent IVF cycle with a sensitivity of 80% and a specificity of 85%. In 2008, Riggs and colleagues confirmed that AMH concentrations correlated the best with the number of retrieved oocytes relative to age, FSH, inhibin B, LH, and estradiol.
High concentrations of AMH can also be present in women with polycystic ovarian syndrome (PCOS), a cause of female infertility. Therefore, in PCOS patientsAMH should not be used alone, but should be combined with transvaginal ultrasound to count the number of follicles.
Women who are diagnosed with diminished ovarian reserve should be counseled regarding options such as oocyte donation or adoption.